title: Effect of chelators on the pharmacokinetics of (99m)Tc-labeled imaging agents for the prostate-specific membrane antigen (PSMA).
abstract: Technetium-99m, the most commonly used radionuclide in nuclear medicine, can be attached to biologically important molecules through a variety of chelating agents, the choice of which depends upon the imaging application. The prostate-specific membrane antigen (PSMA) is increasingly recognized as an important target for imaging and therapy of prostate cancer (PCa). Three different (99m)Tc-labeling methods were employed to investigate the effect of the chelator on the biodistribution and PCa tumor uptake profiles of 12 new urea-based PSMA-targeted radiotracers. This series includes hydrophilic ligands for radiolabeling with the [(99m)Tc(CO)3](+) core (L8-L10), traditional NxSy-based chelating agents with varying charge and polarity for the (99m)Tc-oxo core (L11-L18), and a (99m)Tc-organohydrazine-labeled radioligand (L19). (99m)Tc(I)-Tricarbonyl-labeled [(99m)Tc]L8 produced the highest PSMA+ PC3 PIP to PSMA- PC3 flu tumor ratios and demonstrated the lowest retention in normal tissues including kidney after 2 h. These results suggest that choice of chelator is an important pharmacokinetic consideration in the development of (99m)Tc-labeled radiopharmaceuticals targeting PSMA.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA. sray9@jhmi.edu
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Ray Banerjee
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: Alexander
authors.initials: A
authors.lastname: Falk
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006834:Hydrazines / Q000737:chemistry / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D064847:Multimodal Imaging; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013667:Technetium; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000954:Antigens, Surface; D002614:Chelating Agents; D006834:Hydrazines; D019275:Radiopharmaceuticals; D013667:Technetium; D014508:Urea; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II